Isabelle SALMON, MD, PhD
The main research themes of the department focus on the identification and validation of new biomarkers in human cancers with diagnostic, prognostic and theranostic purposes. The research activities combine fundamental and clinical aspects, with emphasis on quality accreditation of all steps of our analyses. This is why we conduct our investigations from the sample to most advanced technologies in immunohistochemistry (including image analysis) and in molecular pathology. For more than 15 years, our investigations have been focused on biomarkers in human tissue samples, animals and in vitro models. For human tissue samples, biobanking is implemented. Immunohistochemistry (IHC) plays an essential role in the validation of biomarkers because this technology enables morphological control and thus protein localization at histological and cellular levels. A close collaboration with the Laboratory of Image Synthesis and Analysis (LISA, Ecole polytechnique de Bruxelles, U.L.B., www.lisa.ulb.ac.be) enables us to develop standardized tools for characterizing protein expression by using the multiple abilities provided by digital image analysis. From this collaboration was created the interfaculty unit, DIAPath (Digital Image Analysis in Pathology), which is included in the Center for Microscopy and Molecular Imaging (CMMI, Biopark of Gosselies, www.cmmi.be). More recently, international efforts to catalogue mutations for multiple forms of cancer, coupled with the successes of targeted agents in patients with molecularly defined tumors, have generated enthusiasm for incorporating genomic profiling into clinical cancer practice. The department has developed a molecular pathology lab allowed us the study of new genomic biomarkers.
The figure describes the organization of the Department.
I) Identification of morphological and immunohistochemical biomarkers in oncology
Identification of biomarkers related to angiogenesis in oncology
Role of IGF-IIR/Man-6-P in angiogenesis
Glioblastomas (GBM) are the most common and aggressive primary malignant brain tumours in adults. One of their histopathological hallmarks is the microvascular proliferation. This led to the development of anti-angiogenesis targeted therapies against VEGF which is the major actor of angiogenesis in all tumours. Unfortunately, resistance towards these anti-VEGF therapies has been well described. One of the hypotheses to explain this resistance is the activation/upregulation of other signaling pathways. Insulin-like growth factor-II/Mannose-6-phosphate receptor (IGFIIR/Man-6-P) is a receptor that belongs to the insulin like growth factor (IGF) system. The involvement of IGF-IIR/Man-6-P in the process of angiogenesis has been suggested in some rare studies. There are, however, no data on a potential role of IGF-IIR/Man-6-P in the neovascularisation of human GBM. We study a possible involvement of IGF-IIR/Man-6-P in the process of angiogenesis using human GBM and other cancer samples, their normal counterparts and in vitro models.
Role of myofibroblasts in the recurrence of rectal cancer treated by neoadjuvant
Characterization of peritumoral stromal cells in in-situ and invasive breast carcinoma.
II) Identification of molecular biomarkers in oncology
Impact of Molecular Screening by Next Generation Sequencing in Management of Patients with Thyroid Nodules
Unnecessary surgery for patients with cytologically indeterminate thyroid nodule after fine-needle aspiration (FNA), but later found to be benign remains a substantial health-care problem. Clinical, immunohistochemical or molecular variables have been proposed to characterize the benign versus malignant nature of thyroid nodules. Many molecular markers could offer diagnostic information for thyroid lesions. Recently, a new technology, next generation sequencing (NGS), has emerged for gene panel sequencing. FNA specimens can be analyzed by NGS, although this approach needs further improvement to be integrated in daily practice. We propose to evaluate the additive contribution brought by molecular characterization in the diagnosis of indeterminate FNA. We are developing a NGS gene panel in order to offer a testing covering the main molecular alterations observed in thyroid cancer. We plan to submit clinical, cytological and molecular data to decision tree methods in order to develop an algorithm for surgical indication of patients with indeterminate FNA.
Molecular classification of gliomas
Gliomas and Glioblastomas (GBMs) exhibit considerable variability in biological behavior, resulting in significant differences in terms of prognosis and response to treatment. In an attempt to better understand the biology of GBM, many groups have performed high-scale profiling studies based on gene or protein expression. These studies have revealed the existence of several GBM subtypes. Although there remains to be a clear consensus, two to four major subtypes have been identified. Interestingly, these different subtypes are associated with both differential prognoses and responses to therapy. In the present project, we plan to investigate an alternative approach to achieve a molecular classification for gliomas and GBM using immunohistochemistry and targeted next generation sequencing.
HPV genotyping and characterization in anogenital and ORL lesions (in collaboration with the Belgian HPV reference center)